Many individuals with chronic spinal cord injury (SCI) face the challenge of managing their unstable blood pressure which frequently results in persistent hypotension due to decreased cardiac output and autonomic nervous system dysfunction. In addition, blood pooling in the lower body during upright posture leads to a further decrease in blood pressure known as orthostatic hypotension. These conditions severely impact the overall health of SCI individuals, delay their participation in rehabilitative treatment, limit the effectiveness of such treatment, and significantly interfere with activities of daily living. In our clinic that utilizes activity-based therapy programs, we have observed that one of the most common impediments to full participation in these programs was orthostatic hypotension. Further, orthostatic intolerance increases the cost and decreases the efficacy of rehabilitative treatment. Another common impediment to rehabilitation after SCI is respiratory insufficiency due to paresis and paralysis of respiratory muscles. Physiologically, these respiratory and cardiovascular dysfunctions are closely related. Data from our laboratory show that resting blood pressure correlates positively with pulmonary function outcomes and the location and severity of spinal cord lesion. These relationships could be due to better venous return to the heart as a result of higher negative intrapleural pressure and/or higher sympathetic tone due to better baroreflex response in individuals with better inspiratory and expiratory motor control. Our preliminary data showed that respiratory motor function after SCI can be improved by respiratory muscle training (RMT), a rehabilitative technique based on the breathing with resistance exercise. We observed that resting blood pressure and orthostatic tolerance were also improved after RMT in individuals with SCI. Therefore, for the current proposal, we hypothesize that RMT will improve blood pressure regulation in individuals with chronic SCI. We will examine the response of physiological regulatory mechanisms to RMT. Based on statistical power analysis, forty five individuals who have chronic SCI will be recruited for this study over a four-year period. All subjects will have been diagnosed as having respiratory function deficits and orthostatic hypotension. We will evaluate pulmonary and cardiovascular function using spirometry, respiratory muscle strength, sympathetic skin response tests, and surface electromyography of respiratory muscles. In addition, we will use continuous beat-to-beat recording of systemic arterial blood pressure, heart rate, cardiac output, and the measurements of blood catecholamines level during orthostatic stress test. Autonomic regulation outcomes will be calculated from beat-to-beat blood pressure and heart rate frequency composition analysis. We will also evaluate Spinal Cord Injury Independence (SCIM-III) and quality of life (CHART) measures. These outcomes will be obtained before a total of 20 RMT sessions lasting 45 minutes each / 5 days per week, immediately after RMT, and during 6-month follow-up period in 35 research participants forming the experimental group. Another 10 individuals, serving as a control group, will undergo the same procedures, except the RMT intervention, during the same time course. This technique as a therapeutic intervention in order to improve the blood pressure regulation and investigate its mechanisms in individuals with SCI has never been tested before. The results of this study will have direct effect on the SCI population by improving our understanding of the mechanisms of pulmonary function and blood pressure regulation and offering a pathophysiologically based rehabilitation strategy. PUBLIC HEALTH RELEVANCE: Spinal cord injury (SCI) is commonly associated with paralysis resulting in pulmonary and cardiovascular dysfunctions which are listed among the leading causes of death in SCI population. The overall goal of this project is use a respiratory to muscle training to enhance respiratory motor function, improve blood pressure regulation, and to investigate the mechanisms of such improvement in persons with chronic SCI. The results of this study will have direct effect on the SCI population by providing the opportunity to significantly improve the overall health in individuals with SCI using novel rehabilitative approaches.